Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months
29. června 2015 aktualizováno: Hospira, now a wholly owned subsidiary of Pfizer
A Phase II, Randomized, Open-Label, Single Center, Pharmacokinetic and Pharmacodynamic Study of Dexmedetomidine in Pediatric Subjects Aged 12 Months Through <24 Months
The purpose of this study is to investigate the pharmacokinetic, pharmacodynamic, and safety of dexmedetomidine at 2 different dose levels in pediatric subjects, aged 12 months through <24 months, administered as an intravenous loading dose followed by continuous infusion for a minimum of 6 hours and up to 24 hours in an intensive care setting.
Přehled studie
Detailní popis
Phase II, randomized, open-label, single-center, study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects across two dose levels (Dose Level 1 consists of a 0.7 mcg/kg loading dose immediately followed by a 0.5 mcg/kg/hr maintenance infusion; Dose Level 2 consists of a 1.0 mcg/kg loading dose immediately followed by a 0.75 mcg/kg/hr maintenance infusion).
The study population will consist of intubated and mechanically ventilated pediatric subjects who require sedation in an intensive care setting for a minimum of 6 hours but not to exceed 24 hours.
Subjects eligible for enrollment are 12 months to <24 months of age.
Typ studie
Intervenční
Zápis (Aktuální)
5
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Spojené státy, 15224
- Children's Hospital of Pittusburgh of UPMC
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
1 rok až 1 rok (Dítě)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Subject is 12 months to <24 months of age at screening.
- Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
- Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
- The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.
Exclusion Criteria:
Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:
- Diminished consciousness from increased intracranial pressure
- Extensive brain surgery (surgery requiring intracranial pressure monitor)
- Diminished cognitive function per Principal Investigator (PI) discretion
- Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
- Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.
- Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.
- Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.
- Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.
- Subject who have acute thermal burns involving more than 15 percent total body surface area.
- Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.
- Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.
- Subjects with a life expectancy that is <72 hours.
- Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.
- Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.
- Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).
- Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.
- Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Dose level 1
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
|
For sedation according to protocol
|
|
Experimentální: Dose level 2
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
|
For sedation according to protocol
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC0-∞)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Observed Peak Plasma Concentration (Cmax)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Maximum observed concentration of dexmedetomidine in plasma
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Steady State Concentration (Css)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Concentration of dexmedetomidine at steady state in plasma
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Terminal Elimination Half-life (t1/2)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Terminal elimination half-life of dexmedetomidine.
Half-life is the time required for plasma concentration of the drug to decrease by 50%.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Time to Reach Maximum Plasma Concentration (Tmax)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Weight-Adjusted Plasma Clearance (CLw)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Plasma Clearance (CL)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Clearance of dexmedetomidine after intravenous administration.
Clearance is the rate at which the drug is removed from the plasma after the dose.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Volume of Distribution (Vd)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Volume of distribution of dexmedetomidine after intravenous administration.
Volume of distribution measures how much the drug spreads through the body after the dose.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Weight-Adjusted Volume of Distribution (Vdw)
Časové okno: 30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Average Total Faces, Legs, Activity, Cry, and Consolability (FLACC) Score
Časové okno: Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanyl
|
FLACC scale is a 5 category observational measure to assess pediatric pain on face, legs, activity, cry and consolability.
Responses in each category are scored between 0 to 2 (0 = normal, relaxed to 2 = upset, rigid), for a maximum total score of 10.
|
Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanyl
|
|
Absolute Time That Subject is in UMSS Range 2-4 During Treatment Period
Časové okno: During the treatment (6 to 24 hours)
|
The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper physical stimuli); Score 4 (unarousable). The UMSS scores obtained just prior the loading dose (LD) and 5 and 10 minutes during LD; 0, 5, 10, 15, 30, and 60 minutes and thereafter every 4 hours of the maintenance infusion; within 5 minutes of obtaining each pharmacokinetic sample; within 5 minutes prior and after any midazolam rescue during dexmedetomidine infusion period. |
During the treatment (6 to 24 hours)
|
|
Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
Časové okno: During the treatment (6 to 24 hours)
|
Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion
|
During the treatment (6 to 24 hours)
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Vyšetřovatelé
- Vrchní vyšetřovatel: Constantinos Chrysostomou, MD, Children's Hospital of Pittusburgh of UPMC
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. června 2011
Primární dokončení (Aktuální)
1. srpna 2011
Dokončení studie (Aktuální)
1. srpna 2011
Termíny zápisu do studia
První předloženo
20. června 2011
První předloženo, které splnilo kritéria kontroly kvality
22. června 2011
První zveřejněno (Odhad)
23. června 2011
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
24. července 2015
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
29. června 2015
Naposledy ověřeno
1. června 2015
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Fyziologické účinky léků
- Adrenergní látky
- Neurotransmiterové látky
- Molekulární mechanismy farmakologického působení
- Depresiva centrálního nervového systému
- Agenti periferního nervového systému
- Analgetika
- Agenti smyslového systému
- Analgetika, nenarkotika
- Agonisté adrenergních alfa-2 receptorů
- Adrenergní alfa-agonisté
- Adrenergní agonisté
- Hypnotika a sedativa
- Dexmedetomidin
Další identifikační čísla studie
- DEX-11-01
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na Bolest
-
Liu JiuhongDokončenoRebound Pain | Lipozomální bupivakainČína
-
University of VirginiaZatím nenabírámeArtroplastika ramene | Interscalene Block | Rebound PainSpojené státy
-
Karaman Training and Research HospitalDokončeno
-
Ajou University School of MedicineNábor
-
Beijing Sport UniversityZatím nenabírámePatellofemoral Pain, PFP
-
Beijing Sport UniversityZatím nenabíráme
-
Pamukkale UniversityZatím nenabírámePatellofemoral Pain, PFPTurecko (Türkiye)
-
Beijing Sport UniversityDokončenoPatellofemoral Pain, PFPČína
-
Istanbul University - CerrahpasaNáborPatellofemoral Pain, PFPTurecko (Türkiye)
-
The First Affiliated Hospital of Xiamen UniversityNáborRebound Pain | Artroskopická operace kolena | OliceridinČína